Our long-term objective has been to develop a set of noninvasive techniques for studying the human retina. By applying novel techniques and current theories of phototransduction to the full-field electroretinogram (ERG), we have successfully developed widely-used noninvasive techniques for studying the global activity of the rod and cone receptors, as well as the rod bipolar cells. However, many of the planned and/or anticipated clinical trials involving diseases of the receptors require localized measures of retinal function for evaluating treatment efficacy. In the past, we have worked with the two most popular techniques for measuring local retinal activity, the multifocal electroretinogram (mfERG) and, static automated perimetry (SAP), the behavioral measure of local sensitivity of the visual field. Because these techniques have severe limitations for use in clinical trials, we have turned to a new noninvasive technique for measuring the structure (anatomy) of the retina, frequency domain optical coherence tomography (fdOCT). As part of Aim 1, we intend to explore the relationship between a fdOCT measure of the loss of receptors and the loss of visual function, as measured with SAP and mfERGs, in corresponding regions of the field. These data will allow for the testing of hypotheses about the functional consequences of different genetic types of retinitis pigmentosa (RP) and other types of retinal degenerative diseases. A quantitative comparison of the fdOCT measures to visual field loss will allow us to evaluate the utility of the fdOCT for use in clinical trials. Therapeutic and prosthetic approaches to the treatment of diseases of the receptors depend upon viable post-receptor cells, especially retinal ganglion cells (RGCs) and their axons. Current techniques are not able to make this assessment in patients with diseases of the receptors, as they depend upon functioning receptors. As part of Aim 2, we will assess the structural integrity of post receptor cells, especially (RGCs) and their axons using fdOCT. In addition, to better understand these measurements, patients will be studied with a different noninvasive technique for measuring retinal anatomy, scanning laser polarimetry. Finally, as part of Aim 3, we develop a unique approach and generate a unique data set for evaluating the performance of commercial fdOCT machines and computer software, which purport to measure specific retinal layers. PUBLIC HEALTH RELEVANCE: Many retinal diseases cause blindness by attacking the photoreceptors while others attack post-receptor cells. We are developing noninvasive techniques for assessing the mechanisms by which a disease affects different retinal cells. These same techniques can enable the ophthalmologist to monitor the health of these cells and, thus the effectiveness of alternative treatments.